Dynamic Contrast-Enhanced Computed Tomography Imaging Biomarkers Correlated With Immunohistochemistry for Monitoring the Effects of Sorafenib on Experimental Prostate Carcinomas
Bibliographic record
Abstract
OBJECTIVES: To investigate dynamic contrast-enhanced computed tomography (DCE-CT) for monitoring the effects of sorafenib on experimental prostate carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation. MATERIAL AND METHODS: Prostate carcinoma allografts (MLLB-2) implanted subcutaneously in male Copenhagen rats (n=16) were imaged at baseline and after a 1-week treatment course of sorafenib using DCE-CT with iopromide (Ultravist 370, Bayer Pharma, Berlin, Germany) on a dual-source 128-slice CT (Somatom Definition FLASH, Siemens Healthcare, Forchheim, Germany). Scan parameters were as follows: detector width, 38.4 mm; contrast agent volume, 2 mL/kg bodyweight; injection rate, 0.5 mL/s; scan duration, 90 seconds; and temporal resolution, 0.5 seconds. The treatment group (n=8) received daily applications of sorafenib (10 mg/kg bodyweight) via gavage. Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min), endothelial permeability-surface area product (PS, mL/100 mL/min), and tumor vascularity (plasma volume, %) were calculated using a 2-compartment uptake model. DCE-CT parameters were correlated with immunohistochemical assessments of tumor vascularity (RECA-1), cell proliferation (Ki-67), and apoptosis (TUNEL). RESULTS: Sorafenib significantly (P < 0.05) suppressed tumor perfusion (25.1 ± 9.8 to 9.5 ± 6.0 mL/100 mL/min), tumor vascularity (15.6% ± 11.4% to 5.4% ± 2.1%), and PS (8.7 ± 4.5 to 2.7 ± 2.5 mL/100 mL/min) in prostate carcinomas during the treatment course. Immunohistochemistry revealed significantly lower tumor vascularity in the therapy group than in the control group (RECA-1; 181 ± 24 vs. 314 ± 47; P < 0.05). In sorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 7132 ± 3141 vs. 3722 ± 1445; P < 0.05) and significantly less proliferating cells (Ki-67; 9628 ± 1.298 vs. 17,557 ± 1446; P < 0.05) were observed than those in the control group. DCE-CT tumor perfusion correlated significantly (P < 0.05) with tumor cell proliferation (Ki-67; r=0.55). DCE-CT tumor vascularity correlated significantly (P < 0.05) with immunohistochemical tumor cell apoptosis (TUNEL; r=-0.59) and tumor cell proliferation (Ki-67; r=0.68). DCE-CT endothelial PS correlated significantly (P < 0.05) with immunohistochemical tumor cell apoptosis (TUNEL; r=-0.6) and tumor vascularity (RECA-1; r=0.53). While performing corrections for multiple comparisons, we observed a significant correlation only between DCE-CT tumor vascularity (RECA-1) and tumor cell proliferation (Ki-67). CONCLUSION: Sorafenib significantly suppressed tumor perfusion, tumor vascularity, and PS quantified by DCE-CT in experimental prostate carcinomas in rats. These functional CT surrogate markers showed moderate correlations with antiangiogenic, antiproliferative, and proapoptotic effects observed by immunohistochemistry. DCE-CT may be applicable for the quantification of noninvasive imaging biomarkers of therapy response to antiangiogenic therapy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".